Brain serotonin dysfunction is implicated in a range of heritable diseases including alcoholism, mood disorders, eating and obsessive- compulsive (OCD) disorders. An important starting point for understanding innate vulnerability to such diseases is to identify variation in genes involved in serotonin function. The 5-HT2A receptor gene is thought to contribute to appetitive behaviors and to anxiety, and is one site of action of antipsychotics, hallucinogens and anti- depressants. 5-HT2A receptor densities are higher in individuals with depression and suicide attempts. In this study we replicated an earlier finding of an association of the 5-HT2A promoter polymorphism -1438G/A with anorexia nervosa. In addition we showed that the association extends to OCD but not to bulimia nervosa, a disorder in which obsessive and perfectionistic traits are less manifest (Enoch et al 1998).We have now shown that the promoter polymorphism is associated with OCD in women but not men. We have also demonstrated that this 5- HT2A polymorphism is associated with a particular personality type: low novelty seeking and high harm avoidance, again in women but not in men. We have shown an association of the -1438A variant allele with Seasonal Affective Disorder, a condition in which depression recurs in the winter and remits in the spring (Enoch et al 1999). Preliminary results show an association of this variant with major depression found in community populations but not with major depression found in populations with a high prevalence of severe alcoholism. Association studies are being completed in other data sets and preparations are being made for functional studies of this promoter polymorphism. - genetics, serotonin receptor, association, anorexia nervosa, obsessive- compulsive disorder, depression.